Prof Anand Pillai: Case Series #2

Critical Intervention Case Series #2

A Novel Surgical Revision with Custom Implant and Local Prophylactic Antibiotic Delivery Regime Following Failed 2-Stage Ankle Fusion with Osteomyelitis

By Anand Pillai and Team at University Hospitals South Manchester, Wythenshawe

Anand Pillai, Consultant Orthopaedic and Trauma Surgeon

(This article appeared in Foot Print, the Bulletin of the British Orthopaedic Foot and Ankle Society, in January 2025.)

Abstract
Osteomyelitis is a challenging-to-treat infection caused by pyogenic organisms including bacteria, fungi and mycobacteria; characterised by progressive inflammatory destruction, necrosis and neoformation of bone tissue. Pathophysiology of osteomyelitis is multifactorial, involving complex interplay between microbial pathogens, host immune defence mechanisms and tissue damage. Annual incidence of paediatric and adult osteomyelitis is approximately 13 and 90 per 100,000 individuals, respectively.[1,2] Incidence is reportedly higher in men, for reasons unknown, and increases with age, reportedly due to increased prevalence of comorbidity such as diabetes mellitus and peripheral vascular disease.[3]

The Waldvogel classification is the most widely adopted model in clinical studies; osteomyelitis is differentiated according to mechanism of bone infection and duration of infection.[4]  Osteomyelitis may result from hematogenous bacterial seeding from an otherwise distant source of infection, originate from contiguous microbial spread from directly adjacent soft tissues, via direct inoculation as a consequence of trauma or surgery, or be associated with peripheral vascular insufficiency. Immunocompromised states, including diabetes mellitus. HIV and immunosuppressive therapy increase susceptibility to osteomyelitis by impairing host defence mechanisms against microbial pathogens.[5]

Infections following surgical stabilisation of fractures or joint replacement are devastating complications and extremely difficult to treat. Orthopaedic hardware and osteo-inductive grafts alter the immediate environment, including local immunity, favouring bacterial invasion; providing privileged space for bacteria to reside, and a home for biofilm formation with potential to rapidly develop antimicrobial resistance and expression of virulence factors.[6] Eradication of infection with systemic medication is particularly challenging; the emergence of drug-resistant strains, such as methicillin-resistant S. aureus (MRSA), results in challenging complexities for infection control and hospital endemics.[7]

Once a prosthesis-associated infection has been diagnosed, proper management is paramount to eradicate the infection and maximise residual function of the joint. This often requires a multi-disciplinary approach involving antimicrobial therapy, surgical intervention and adjunctive measures to promote bone healing.[8] Initial antibiotic therapy for infection is often empiric and should be initiated promptly, guided by suspected pathogens and their antibiotic susceptibility profile.[9] Once microbiology results have been determined, adjustments can be made based on culture and sensitivity to greater definitive treatment. Antimicrobials should be administered for a minimum of four weeks, but ideally six weeks.[10]

However, the Short or Long Acting Regimes in Orthopaedics (SOLARIO) study[11] reported that, in the presence of local antibiotics, a short regime (≤7 days) of systemic antibiotics was non-inferior to 4 weeks of systemic antibiotics when treating orthopaedic infection. In addition, there were substantially fewer side effects with a short regime (≤7 days) of systemic antibiotics. The study concluded that local antibiotic delivery would benefit patients, limit resistance selection, and thereby improve antimicrobial stewardship.

Surgical treatment is the gold standard for prosthetic joint infections.[12] Surgical debridement and drainage are essential for removing necrotic tissue and establishing adequate local antibiotic delivery, particularly in cases of chronic or refractory osteomyelitis.[13] In severe cases, limb salvage procedures such as bone grafting, vascularised bone flaps, and replacement may be necessary. Adjunctive measures such as hyperbaric oxygen therapy, local antibiotic delivery systems, and biofilm-disrupting agents may also be considered in select cases to augment the effectiveness of treatment.[13]

One such adjunctive agent is ArthroZheal®, an autologous, biocompatible, bioactive, platelet - rich fibrin (PRF) matrix which seals, heals, and accelerates the regeneration of tissue such as cartilage, meniscus, tendons, and ligaments. Once the active concentrate is prepared, the contents are secured within the patented applicator, and the thrombin-free concentrate is then simultaneously applied with a pH-balancing re-coagulant as a flow-controlled, easily directed and deployed micro-particulate spray, which polymerises instantly upon contact with the target tissue, or synthetic prostheses or implant, even in a fluid environment (Fig. 1). Once applied to the target tissue, regardless of the orientation of the application site – horizontal or vertical – or the localised degree of moisture, the bioactive matrix acts as an intra-operative haemostat, a stable and non-displacing polymeric matrix to potentiate tissue sealing, and a growth factor-rich reparative micro-environment which optimises healing in compromised tissue.

Fig 1 ArthroZheal Coated Bone Graft

ArthroZheal® can be simultaneously deployed in conjunction with high potency liquid antibiotics such as Gentamicin, which then elutes gradually from the fibrin matrix over time, thus impeding localised bacterial infection and the formation of biofilm on prostheses and implants.  

Methodology
A 62 year old male was referred following an open ankle fracture-dislocation 2 years previously  (Fig.2). The patient had no past medical history, did not smoke and was an active 59-year-old at the time of his injury. He was initially treated with a debridement and open reduction internal fixation (Fig. 3), which became infected at 5 weeks post-op’, and subsequently underwent removal of metalwork + debridement + external fixator (Fig. 4a+b). Later a staged fusion was performed via an Ilizarov frame (Fig. 5a+b). This failed with non-union and persistence of infection and progressive deformity.  

Fig 2 Right Ankle XRS at time of referral

Fig 3 Intra-op ORIF images

Fig 4a_b Before and after External Fixator Removal

Fig 5a+b AP and lateral XRs of Ilizarov frame fusion

The patient underwent a 2-stage limb salvage undergoing an initial debridement + cement spacer (Fig. 6) followed by a hind foot fusion using a custom 3D printed cage and nail (designed from CT scans of the ankle) (Fig. 7). The patient was treated for osteomyelitis after intra-operative samples grew Staph epidermidis and Staph pseudintermedius. 

Fig 6 Intra-op images of debridement + cement spacer

Fig 7 Intra-op image of second stage TTC fusion with cage and hindfoot nail

During the second stage procedure, the cement spacer was removed, bone ends re-cut using bespoke cutting jigs and bone graft harvested using a reamer-irrigator-aspirator (RIA) from the femoral canal. The bone graft was packed into the cage and coated in ArthroZheal® combined with antibiotics (Gentamicin) to prophylactically protect against infection and biofilm. The cage was then placed within the pre-prepared proximal and distal margins and secured using hind foot nail and screws. 
There was no loss in position.

The patient was pain free following recovery and remained so until discharge from hospital. He was reviewed by the author at 2 weeks, 6 weeks, and 10 weeks. Weightbearing and rehabilitation commenced at 12 weeks post-operatively, there were no indications or symptoms of local infection at any point. The use of ArthroZheal® as a topical medium to enhance both bone and soft tissues healing, as well as a durable, bio-assimilable vehicle for antibiotic delivery, ensured an optimal environment for a successful outcome, and CT scan showed full incorporation at 3 months post-operatively. (Fig. 8)

Fig 8 Cage fully incorporated 3 months post-op

 

References

1. Riise, Ø.R. et al. (2008) ‘Childhood osteomyelitis-incidence and differentiation from other acute onset musculoskeletal features in a population-based study’, BMC Pediatrics, 8(1). doi:10.1186/1471-2431-8-45.
2. Henke, P. (2006) ‘Osteomyelitis of the foot and toe in adults is a surgical disease’, Annals of Surgery, 243(3), p. 430. doi:10.1097/00000658-200603000-00028.
3. Momodu, I.I. (2023) Osteomyelitis, StatPearls [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK532250/ (Accessed: 03 April 2024).
4. Lima, A.L. et al. (2014) ‘Recommendations for the treatment of osteomyelitis’, The Brazilian Journal of Infectious Diseases, 18(5), pp. 526–534. doi:10.1016/j.bjid.2013.12.005.
5. Khan, K. et al. (2015) ‘Sternoclavicular osteomyelitis in an immunosuppressed patient: A case report and review of the literature’, American Journal of Case Reports, 16, pp. 908–911. doi:10.12659/ajcr.895803.
6. Hellwinkel, J.E. et al. (2022) ‘The intersection of Fracture Healing and Infection: Orthopaedics Research Society Workshop 2021’, Journal of Orthopaedic Research, 40(3), pp. 541–552. doi:10.1002/jor.25261.
7. Tarai, B., Das, P. and Kumar, D. (2013) ‘Recurrent challenges for clinicians: Emergence of methicillin-resistant Staphylococcus aureus, vancomycin resistance, and current treatment options’, Journal of Laboratory Physicians, 5(02), pp. 071–078. doi:10.4103/0974-2727.119843.
8. Besal, R. et al. (2023) ‘Systemic antimicrobial treatment of chronic osteomyelitis in adults: A narrative review’, Antibiotics, 12(6), p. 944. doi:10.3390/antibiotics12060944.
9. Leekha, S., Terrell, C.L. and Edson, R.S. (2011) ‘General principles of antimicrobial therapy’, Mayo Clinic Proceedings, 86(2), pp. 156–167. doi:10.4065/mcp.2010.0639.
10. Mader JT, Shirtliff ME, Bergquist SC, Calhoun J. Antimicrobial treatment of chronic osteomyelitis. Clin Orthop. 1999(360):46-65
11. Dudareva, M., Kümin, M., Vach, W. et al. Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO): a randomised controlled open-label non-inferiority trial of duration of systemic antibiotics in adults with orthopaedic infection treated operatively with local antibiotic therapy. Trials 20, 693 (2019). https://doi.org/10.1186/s13063-019-3832-3
12. Kaufman, M., Meaike, J. and Izaddoost, S. (2016) ‘Orthopedic prosthetic infections: Diagnosis and orthopedic salvage’, Seminars in Plastic Surgery, 30(02), pp. 066–072. doi:10.1055/s-0036-1580730
13. Calhoun, J., Manring, M.M. and Shirtliff, M. (2009) ‘Osteomyelitis of the Long Bones’, Seminars in Plastic Surgery, 23(02), pp. 059–072. doi:10.1055/s-0029-1214158.